Jasper?s Basic Mechanisms of the Epilepsies Workshops SUMMARY Every decade, the Jasper?s Basic Mechanisms of the Epilepsies (BME) Workshops provide an opportunity for basic research scientists in epilepsy to assess where the field of epilepsy has been, what it has accomplished, and where it should go. Four workshops have been held since the late 1960?s; the last held at Yosemite Lodge in 2009. Ten years have passed, and it is once again time to stimulate a new intellectual ferment in understanding genetic, molecular, cellular and systems mechanisms of epilepsies and link these discoveries to the development of novel treatments for the nearly one third of persons who are resistant to current therapy. Like its predecessor, the fifth BME Workshops will be held over four days in the spring of 2019. The PI and co- chairs are responsible for their organization and editing the resulting publication, whose nearly 110 chapters will be widely available through free download on NIH Bookshelf. A major goal of these Workshops is to bridge translation of epilepsy disease mechanisms into molecular epilepsy therapeutics. The specific objectives are to: (1) Accelerate discovery of the genome of common epilepsies and rare/orphan epilepsies and unravel their disease producing mechanisms. (2) Stimulate translation of disease mechanisms of epilepsies into molecular therapeutics against epileptogenesis. Explore individualized pharmacogenomics, gene/iRNA and stem cell therapy and other approaches that constitute cures and repairs for the epilepsies. (3) Recruit new talent and optimize available talent in this field by promoting the involvement of young investigators, women, minorities and persons with disabilities. The general objectives of the fifth BME Workshops remain the same as for the previous four Workshops: capture the most decisive advances in the field, and define new areas and strategies that should be accelerated in the next decade of epilepsy research. The 2019 Workshops will set as an overarching goal to stimulate the development of cures and repairs for the epilepsies and thereby decrease the prevalence and incidence rates of this disease. To accomplish these objectives, the Workshops will strive to: (1) Collect and synthesize recent understanding and identify gaps of knowledge in the initiation, spread and arrest of seizures, (2) Develop consensus on the initial changes in brain network plasticity leading to epileptogenesis after genetic and environmental insults (e.g. prolonged febrile seizures, repeated seizures, birth anoxia- hemorrhage, head trauma, infection, stroke, and aging). (3) Identify more Mendelian epilepsy genes and Non- Mendelian epistatic modifiers responsible for common epilepsies as well as resistance to seizures. (4) Unravel the pathogenic mechanisms of these monogenic disorders and design optimal treatments. (5) Change the culture of anticonvulsant drug development directed against seizures toward earlier detection of risk for epilepsy and exploring the biology and antiepileptogenic treatments designed to cure and repair epilepsies, and (6) Recruit and inspire the next generation of new and diverse scientific talent to lead this endeavor.